Acute lung injury (ALI), and its severe form, acute respiratory distress syndrome (ARDS), are devastating conditions that affect approximately ˜200,000 persons per year in the United States and represent ˜10% of intensive care unit admissions worldwide (1,2). Despite advancements in intensive care, mortality from ALI/ARDS remains high, reaching 35-40%. ALI/ARDS is a type of pathologic inflammation, whereby injury to the lungs may be due to an initial insult elsewhere in the body, leading to activation of the immune system (inflammation). In fact, approximately 30% of patients with ARDS have extra-pulmonary causes. One such example is secondary ALI/ARDS because of the inflammatory state of sepsis (3-5) (reviewed in (6)).
Integral to the initiation of inflammation is the interaction and adhesion of leukocytes to platelets and vascular endothelium. These early steps are mediated through cell surface adhesion molecules on the leukocytes to counter-receptors on platelets and endothelium (7-12). In most cases, the presence of inflammation plays an important role in the maintenance of health, such as in infection (5) and wound healing (13). However, in pathologic inflammation, these processes may lead to tissue injury and organ dysfunction at sites distant from the initial insult. Therefore, blocking leukocyte recruitment into otherwise healthy organs could have a beneficial role in attenuating pathologic inflammation, such as ALI and ARDS.
The present disclosure provides a solution to the need for treatment of certain medical conditions, including at least ALI and ARDS, for example.